Inhalable Lung Cancer Drug Delivery Performs Well, Study Suggests

The powerful anticancer drug interleukin-12 was delivered more safely to lungs via inhalation in mouse models.
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In a twist of irony, a powerful drug that battles lung cancer might be delivered safer via inhalation versus surgery, injection, and other invasive methods, a new study suggests.

Researchers associated with Columbia University observed rat models and determined that a new inhalable lung cancer treatment is capable of delivering localized immunotherapy to difficult-to-treat tumors.

Lately researchers have been looking for a safe and non-invasive alternative to current approaches to tackling cancerous tumors that require direct injection of immunomodulators into the tumors. But when cancer is found in the lungs, it is typically hard to reach and treat with drugs by direct injection.

Researchers believe that a potent drug that fights cancer might be better delivered via inhalation in order to battle lung cancer. The study was published recently in Nature Nanotechnology and online Jan. 11, showing how nanobubbles containing a powerful drug could be administered via inhalation to provide a safer delivery route. 

Medscape reports that researchers demonstrated that nanobubbles can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation. Researchers suspect that exosomes, also known as extracellular vesicles (EVs), could be the key to the next step in lung cancer treatment.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia, who has been working with stem cells and exosomes for over 15 years. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

The study could help move research forward by allowing for the therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Researchers have known about IL-12’s abilities to fight cancer for decades, but early human trials lead to serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. The research team’s new approach involves inserting mRNA for IL-12 into exosomes.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

In the study, researchers developed inhalable extracellular vesicles loaded with IL-12 mRNA to battle lung cancer and bolster systemic immunity in mice with tumors. IL-12 mRNA was loaded into human embryonic kidney cell-derived exosomes (HEK-Exo) through electroporation, yielding IL-12 mRNA-loaded exosomes (IL-12-Exo). 

When inhaled by mice with lung tumors, IL-12-Exo outperformed IL-12 mRNA-loaded liposomes (IL-12-Lipo)n and minimized systemic toxicity. These inhaled IL-12-Exo promoted

immune activation, systemic immunity, and immune memory, culminating in lung tumor suppression and heightened resistance against tumor recurrences.

Lung Cancer and Smoking

Human trials could launch within five years, and help put an end to the devastation that lung cancer causes each year. 

Lung cancer is the leading cause of cancer death overall and among both men and women. (The second leading cause of cancer death is prostate for men and breast for women.) In 2021, 134,592 people died from lung cancer, or 22% of all cancer deaths. In the United States, cigarette smoking is linked to about 80% to 90% of lung cancer deaths. 

However, even the Lung Cancer Society notes that while it is not risk-free as it involves combustion, cannabis smoke is not as carcinogenic as tobacco smoke. NORML explains this very well: THC and CBD, the two most popular cannabis active ingredients, are non-carcinogenic and demonstrate anticancer properties in vivo and in vitro. Nicotine—in stark contrast—promotes the development of cancer cells and their blood supply. In addition, cannabinoids stimulate other biological activities and responses that may mitigate the carcinogenic effects of smoke.

People who smoke cigarettes are 15 to 30 times more likely to develop lung cancer or die from lung cancer than people who do not smoke. Even smoking a few cigarettes a day or on occasion increases the risk of lung cancer.

Even if you don’t smoke anything, or only vape, you’re still not off the hook, depending on how hazardous areas are that you live in.

People also get lung cancer from radon, and they usually have no control over the undetectable radioactive gas caused by the natural decay of traces in uranium in rocks and the soil. The U.S. Environmental Protection Agency (EPA)  estimates that radon causes about 21,000 lung cancer deaths each year. 

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